There are 5 million births in the United States each year of which 500,000 are premature. Premature delivery is associated with substantial mortality, morbidity and escalating cost. The complications of premature birth result in substantial respiratory, gastrointestinal, immune and central nervous system morbidity and significant mortality. In particular, effective treatment of respiratory failure in premature infants remains an unsolved problem. Several strategies have been developed to support these infants, including refinements in mechanical ventilation and the use of extracorporeal life support (ECLS) in severe respiratory failure. ECLS is limited to infants >34 weeks gestation for 2-3 weeks, requires systemic heparinization and does not maintain fetal circulation. To circumvent many of these challenges, the development of an artificial placenta in the form of a pump-driven arterio-venous AV-ECLS circuit with access via the umbilical vessels is an appealing alternative. For the last 40 years, many investigators have tried to make an artificial placenta but it has never gone beyond the concept phase because of limited technology. Our laboratory has developed a maternal-fetal sheep model with preliminary data demonstrating the feasibility to address this problem. We aim to further characterize and develop this model to prepare for longer duration experiments. We realize that this is a long term project which will impact substantially upon the care of premature newborns. The goal of this proposal is to develop an animal model in the preterm fetal lamb with full extracorporeal gas exchange via the umbilical vessels and maintenance of hemodynamic stability and normal fetal circulation. The specific aims of this proposal are 1) to develop a prototype arterio-venous ECLS artificial placenta including umbilical vessel access and the techniques necessary to provide fetal support;and 2) to maintain stable fetal circulation during AV- ECLS for 24 hours, with particular attention to identify those factors which will limit practical long-term application. PUBLIC HEALTH RELEVANCE: The complications associated with premature birth remain a major unsolved health problem. We propose development of a mechanical artificial placenta that would allow a premature infant to grow and thrive while avoiding the many complications using conventional treatment. Development of an artificial placenta would revolutionize the care of premature infants.